TY - JOUR
T1 - Spatial Mapping of Hematopoietic Clones in Human Bone Marrow
AU - Young, Andrew L.
AU - Davis, Hannah C.
AU - Cox, Maggie J.
AU - Parsons, Tyler M.
AU - Burkart, Samantha C.
AU - Bender, Diane E.
AU - Sun, Lulu
AU - Oh, Stephen T.
AU - Challen, Grant A.
N1 - Publisher Copyright:
©2024The Authors; Published by the American Association for Cancer Research.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow. SIGNIFICANCE: CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow.
AB - Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., >2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow. SIGNIFICANCE: CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow.
UR - http://www.scopus.com/inward/record.url?scp=85192028187&partnerID=8YFLogxK
U2 - 10.1158/2643-3230.BCD-23-0110
DO - 10.1158/2643-3230.BCD-23-0110
M3 - Article
C2 - 38421682
AN - SCOPUS:85192028187
SN - 2643-3230
VL - 5
SP - 153
EP - 163
JO - Blood cancer discovery
JF - Blood cancer discovery
IS - 3
ER -